Novel role of NADPH oxidase in ischemic myocardium: a study with Nox2 knockout mice

被引:0
作者
Mahesh Thirunavukkarasu
Ram Sudheer Adluri
Bela Juhasz
Samson Mathews Samuel
Lijun Zhan
Anupinder Kaur
Gautam Maulik
Juan A Sanchez
Janet Hager
Nilanjana Maulik
机构
[1] University of Connecticut School of Medicine,Molecular Cardiology and Angiogenesis Laboratory, Department of Surgery
[2] University of Debrecen,Department of Pharmacology
[3] University of Connecticut School of Medicine,Translational Genomics Core, Department of Genetics and Developmental Biology
[4] Harvard Medical School,Department of Radiology
[5] Saint Mary’s Hospital,Department of Surgery
来源
Functional & Integrative Genomics | 2012年 / 12卷
关键词
Ischemic preconditioning; Nox2; NADPH oxidase; Gene expression; Cardioprotection;
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摘要
Several potential sources of reactive oxygen species (ROS) in cells exist. One source is NADPH oxidase, which is especially important for superoxide radical production. Nox2 is a primary regulatory subunit of NADPH oxidase. In the present study, we examined the role of ROS and NADPH oxidase in ischemic preconditioning (IP)-mediated cardioprotection by using Nox2−/− mice. Both wild-type (WT) and Nox2−/− mice were subjected to either 30 min of ischemia followed by 2 h of reperfusion (IR) or IP prior to 30 min ischemia and 2 h of reperfusion. Reduction in left ventricular developed pressure (60.1 versus 63 mmHg), dp/dtmax (893 versus 1,027 mmHg/s), and aortic flow (0.9 versus 1.8 ml/min) was observed in Nox2−/−IPIR compared to WTIPIR along with increased infarct size (33% versus 22%) and apoptosis after 120 min of reperfusion. Differentially regulated genes were demonstrated by comparing gene expression in WTIPIR versus Nox2−/− IPIR hearts. Selected differentially regulated genes such as β-catenin, SRPK3, ERDR1, ACIN1, Syntaxin-8, and STC1 were validated by real-time PCR. Taken together, this is the first report identifying important, differentially expressed genes during ischemic preconditioning in Nox2−/− mice by using microarray analysis.
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页码:501 / 514
页数:13
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共 274 条
  • [31] Shah A(2010)Receptor activation of NADPH oxidases Antioxid Redox Signal 13 467-1484
  • [32] Shattock M(2008)Oxidative innate immune defenses by Nox/Duox family NADPH oxidases Contrib Microbiol 15 164-988
  • [33] Cave AC(2010)Aquaporin-1 expression and angiogenesis in rabbit chronic myocardial ischemia is decreased by acetazolamide Hear Vessel 25 237-H1771
  • [34] Brewer AC(1999)Redox signaling: hydrogen peroxide as intracellular messenger Exp Mol Med 31 53-3950
  • [35] Narayanapanicker A(2009)Angiopoietin-1 induces Kruppel-like factor 2 expression through a phosphoinositide 3-kinase/AKT-dependent activation of myocyte enhancer factor 2 J Biol Chem 284 5592-3642
  • [36] Ray R(2005)Glycogen-synthase kinase3beta/beta-catenin axis promotes angiogenesis through activation of vascular endothelial growth factor signaling in endothelial cells Circ Res 96 308-18126
  • [37] Grieve DJ(2008)Heterozygous disruption of Flk-1 receptor leads to myocardial ischaemia reperfusion injury in mice: application of affymetrix gene chip analysis J Cell Mol Med 12 1284-undefined
  • [38] Walker S(2008)Adeno-sh-beta-catenin abolishes ischemic preconditioning-mediated cardioprotection by downregulation of its target genes VEGF, Bcl-2, and survivin in ischemic rat myocardium Antioxid Redox Signal 10 1475-undefined
  • [39] Shah AM(1990)Amplified RNA synthesized from limited quantities of heterogeneous cDNA Proc Natl Acad Sci U S A 87 1663-undefined
  • [40] Chen W(1998)Reactive oxygen species released from mitochondria during brief hypoxia induce preconditioning in cardiomyocytes J Biol Chem 273 18092-undefined